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Flashcards in Stem Cells Deck (15):
1

What is a stem cell?

-Indefinite Self-Renewal
-Differentiation into different types of cells

2

2 types of stem cells

Embryonic Stem Cells

Tissue Committed Stem Cells (adult or fetal)

3

Types of tissue committed stem cells

-Hematopoeitic (bone marrow)
-Messenchymal (bone marrow)
-Intestinal epithelial stem cells (intestines)
-Skin (Hair follicle)
-Neural stem cells (brain)
-Endothelial Progenitor (bone marrow)

4

Life cycle of Embryonic Stem Cell-ESC

Fertilized egg --> blastocyst --> ES cell colony --> Endoderm/mesoderm/ectoderm

5

What was the TRADITIONAL stem cell dogma?

Pluripotent -> multipotent -> differentiated

(Cannot go the opposite way)

6

What is the modern stem cell dogma?

Differentiated to Pluripotent possible!

7

How to generate human induced pluripotent stem cells?

collect blood --> transducer PBMC's with STEMCCA --> Plate PBMC's onto MEFs --> Pick iPSC colonies

8

What are iPSCs?

Induced pluripotent stem cells that can be generated directly from adult cells

They have been genetically reprogrammed to an embryonic stem cell-like state by being forced to express genes and factors

9

What are ESC?

Embryonic stem cells are pluripotent stem cells derived from the inner cell mass of a blastocyst

10

What are multipotent cells?

They can develop into more than one cell type but are limited

I.e.: adult stem cells and cord blood stem cells

11

Blood cell development process

1) Hematopoietic stem cells (HSC- multipotent from mesodermal)

2)CMP (progenitor cell for granulocytes, monocytes, erythrocytes)

3) MEP- Megakaryocyte Erythroid Precursor cell

4a) Erythroblast --> Red Blood Cells

4b) Megakaryocyte --> Platelets

12

How are platelets generated in Vivo?

Bone Marrow Vascular endothelium produces SDF1 and FGF4 (chemokines) that promote Megakaryocyte homing and adhesion

Endothelial layer is sinusoidal- proplatelets are extended into the vasculature through these gaps

Shear forces cause the distal tip of the proplatelet to bleb off into circulation --> fully realized platelets

IPSC derived megakaryocytes can form these pro-platelets

13

Gene editing to transform mutated stem cells

Use Zinc-finger nuclease to cut out mutated part of the cell leading to corrected molecule

*can be used for sickle cell*

14

3 examples of cell specification

Hepatic
IPSC --> definitive endoderm --> hepatic lineage

Cardiac
IPSC --> cardio-meso --> cardiomyocyte

Neuronal
IPSC --> Neuro/ecto --> Neuron

15

IPSC for drug discovery

Patient with genetic disease --> collect peripheral blood from patient --> reprogramming virus --> reprogram into patient specific iPSC --> genetically identical disease-specific iPSC --> differentiate disease-specific iPSC into target cells --> utilize patient-specific target cells to screen for novel therapeutics