This document is written in english. It contains notes of 6 lectures and summaries of some papers. It also contains many pictures for better understanding. The lectures are about an introduction to ethics, pluripotency, iPSC reprogramming, hematopoietic stem cells, neurobiology, organoids, and epid...
Trends in Stem Cell Biology
Inhoudsopgave
Week 1 Introduction Trends in Stem Cell Biology...................................................................................3
LE1 Ethical Theories: Introduction (Luca Consoli)...................................................................................4
LE2 Epigenetics and pluripotency in mouse embryonic stem cells (Hendrik Marks)..............................5
Different forms of cell potency during development in vivo..............................................................5
Different types of mouse pluripotent cells in vitro (mouse)...............................................................6
How is pluripotency to be tested....................................................................................................7
Application of ES cells.........................................................................................................................7
Molecular mechanisms to maintain pluripotency..............................................................................8
Pluripotency and chromatin structure................................................................................................8
Paper: Prolonged Mek1/2 suppression impairs the developmental potential of embryonic stem
cells.....................................................................................................................................................8
Paper discussion in lecture...............................................................................................................10
LE3 Reprogramming to induced pluripotency and beyond (Jo Huiqing Zhou)......................................13
Paper summary: Resolving cell fate decisions during somatic cell reprogramming by Single-Cell
RNA-Seq............................................................................................................................................13
Paper discussion in lecture...............................................................................................................14
Lecture Reprogramming to induced pluripotency............................................................................16
Stem cell types..............................................................................................................................16
Reprogramming: the change of cell fates.....................................................................................17
Application of iPSCs......................................................................................................................19
LE4 Hematopoietic stem cells...............................................................................................................21
Ethical teaser....................................................................................................................................21
The hematopoietic stem cell............................................................................................................21
Leukemic transformations................................................................................................................22
Allogenic stem cell transplantation..................................................................................................22
Engraftment of stem cells.................................................................................................................23
There are 3 main sources to get stem cells from a donor.............................................................23
Donor selection............................................................................................................................23
Engraftment..................................................................................................................................24
Immunology......................................................................................................................................24
NK cells.........................................................................................................................................24
T cells............................................................................................................................................25
Improvement of therapy needed.....................................................................................................25
, Paper: UM171-expanded cord blood transplant support robust T cell reconstitution with low rates
of severe infections..........................................................................................................................25
More stem cells after UM171 expansion -> more CBs available for transplant............................27
Additional therapies.....................................................................................................................27
LE5 Neurobiology.................................................................................................................................29
What happens to the developing brain inside the womb.................................................................29
Influences on cortical development..............................................................................................29
Monogenic disorders:...................................................................................................................29
Corticogenesis..............................................................................................................................29
Brain organoids.................................................................................................................................30
3D.................................................................................................................................................30
Modeling monogenic neurodevelopment disorders (NDDs)........................................................30
Studying cellular and molecular aspects of human brain development.......................................31
Patterned or non-patterned brain organoids................................................................................31
Application of brain oragnoids......................................................................................................32
Pros vs cons..................................................................................................................................32
Papers (paper in the lecture is not the same as on BS assignment).................................................33
Transplantation of human organoids into mouse brain...............................................................33
LE6 Epidermal stem cells......................................................................................................................34
Skin...................................................................................................................................................34
Epidermal renewal........................................................................................................................34
Skin stem cells..................................................................................................................................34
Potency.........................................................................................................................................34
Locate and tracing stem cells........................................................................................................35
Heritable skin diseases.....................................................................................................................37
Two main known types.................................................................................................................37
Ex vivo gene therapy.....................................................................................................................37
Paper: regeneration of the entire human epidermis using transgenic stem cells............................38
Transplanting holoclones stem cells -> stable formed graft.........................................................38
Safety:...........................................................................................................................................38
From basic skin and stem cell biology to regenerative medicine..................................................39
Other therapeutic applications for somatic skin stem cell expansion and grafting:.....................40
,Week 1 Introduction Trends in Stem Cell Biology
Exam 5 open questions, one from each lecture (Only 5 open questions in 2 hours).
Discussion, group essay, and group presentation on five topics (5 groups per session, up to 5 persons
per group).
1. The morel status of the human embryo
2. Embryonic models derived from pluripotent stem cells
3. Human-animal hybrid studies
4. Induced pluripotent stem cells and adult stem cells
5. Development/ unproven stem cell therapies
Students choose topic most interesting to you, then choose time slot and group you like to enroll,
then do group activities. = 20% of grade (10% group essay and 10% presentation). The time slot
refers to the presentation.
Essays are max 500 words. Every individual has to review 4-5 other essays.
ChatGPT is allowed to improve language (make that clear in the end of your essay). The point of the
essay is to read the literature and make opinions. All essays and reviews will become public in the
end.
, When uploading the presentation, include another slide with and estimated percentage of your
contribution.
LE1 Ethical Theories: Introduction (Luca Consoli)
Not for examination, but tools for how to articulate a discussion.
Ethical subjectivism is the idea that moral opinions are based on our feelings and nothing more.
There is no such thing as objective right and wrong
Ethical theories are a way to explain what makes an action justifiable or not
Ethical theories go beyond particular ethical judgments
Ethics are not the same as morals or the law
Ethical Theories:
- Consequentialism = the rightness/wrongness of an action is determined by its consequences
(action -> result)
o Utilitarianism = the right action is the one that promotes the greatest happiness
o Ethical egoism = the right action is the one that promotes the greatest happiness of
the agent
- Deontology = the rightness/wrongness of an action is determined by inherent features of the
action itself, or by an inherently valid rule (rule -> action)
o If an action is of the wrong kind, it is forbidden , no matter how good its
consequences are (rejects both consequentialism theories) the end doesn’t justify
the means
o Kantianism (Immanuel Kant) = right actions must be universalizable (must be possible
to will the principle of your action for everybody without inconsistency) and must
treat rational agents as ends, not mere means. Mustnt sacrifice the few even to
benefit the many
- Virtue Ethics = the rightness/wrongness of an action is determined by the character traits it
expresses (character -> action). Emphasize what kind of person you should be
o Aristotelianism
o Confucianism
- Contractarianism
- Natural law
- Relativism
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